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Sacubitril/valsartan (LCZ696), an angiotensin receptor neprilysin inhibitor (ARNI), simultaneously inhibits neprilysin and the renin-angiotensin-aldosterone system, but its effects on diet-induced vascular inflammation and atherosclerosis are unclear. LCZ696 (100 mg/kg/day), valsartan (50 mg/kg/day) or hydralazine (10 mg/kg/day) was orally administered to apolipoprotein E-deficient (ApoE-/-) mice for 20 weeks. En-face Sudan IV staining of the aortic arch, quantitative reverse transcription polymerase chain reaction (RT-PCR) of abdominal aorta. There were no differences in metabolic parameters between the groups. Valsartan or LCZ696 significantly reduced the progression of atherosclerotic lesions compared to the hydralazine group, as determined by Enface Sudan IV staining of the aortic arch (p<0.05). In the abdominal aorta, valsartan or LCZ696 treatment reduced mRNA expression of inflammatory molecules. However, no significant difference was observed between the valsartan group and the LCZ696 group regarding these atherosclerotic changes and vascular inflammation. LCZ696 reduced the progression of diet-induced atherosclerotic plaques and vascular inflammation compared with hydralazine in ApoE-/- mice, but showed no difference compared with the valsartan group. J. Med. Invest. 73 : 116-120, February, 2026. Show less

Vascular calcification represents a significant clinical challenge, leading to cardiovascular disease, though its underlying mechanisms remain incompletely understood. Recent studies indicate that Toll-like receptor 9 (TLR9), a key element of innate immunity, plays a pathogenic role in vascular inflammation and atherogenesis. Therefore, we hypothesized that TLR9 signaling promotes vascular chondrogenesis and calcification. We compared apolipoprotein E-deficient (ApoE Show less